Bridging The Atlantic: A European Executive's Guide To Entering The U.S. RNA Market (Pt. 1)

By Ahmet C. Berkyurek, Ph.D., Cofounder & CEO, CamMed Therapeutics Ltd.

Europe has long been a cradle of RNA innovation. From the foundational RNA chemistry developed in academic labs in Germany and the U.K. to the lipid nanoparticle formulation science pioneered in the Netherlands and the clinical programs advancing out of Switzerland, Sweden, and beyond, the continent has earned its place at the forefront of the RNA therapeutics revolution.

Yet for many European RNA companies, the path to full commercial realization inevitably leads west. The United States remains the world’s largest pharmaceutical market, home to the most active venture ecosystem, a highly experienced regulatory agency, and the deepest pool of RNA-specialized talent outside of a handful of European hubs. Entering that market, however, is neither straightforward nor risk free.

For many European RNA companies, expanding into the U.S. represents the next major step toward commercialization. But success requires more than groundbreaking science — it demands a clear strategy for navigating regulatory expectations, securing investment, building partnerships, and establishing a sustainable U.S. presence.

In this two-part series, I share practical insights to help European biotech leaders successfully bridge the Atlantic. Part 1 focuses on regulatory strategy and market entry, while Part 2 explores fundraising, manufacturing, partnerships, and long-term growth.

Regulatory Landscape: FDA Vs. EMA Vs. MHRA

The U.S. FDA, U.K. Medicines and Healthcare Products Regulatory Agency (MHRA), and the European Medicines Agency (EMA) are all rigorous, science-driven regulators, and these agencies have invested significantly in harmonization through the ICH (International Council for Harmonisation) guidelines. For RNA therapeutics, however, meaningful differences in principles, process, and pace create real strategic implications.

Designation Programs And Early Engagement

For RNA modalities where manufacturing processes, delivery systems, and biomarker strategies are still maturing, this iterative engagement is enormously valuable. The FDA’s Breakthrough Therapy designation (BTD), Platform Technology designation program, and Fast Track pathways offer not merely expedited review timelines but, crucially, intensive early and frequent dialogue with the agency. European companies accustomed to EMA’s Scientific Advice process often find FDA interactions more direct and fast-paced.

The EMA’s PRIME (Priority Medicines) scheme is the closest European analogue to BTD, but take-up has been slower, and the depth of regulatory interaction, particularly at the pre-IND or pre-CTA stage, is generally less intensive. This largely reflects the program’s deliberately selective eligibility criteria and the more limited regulatory incentives it offers, rather than an unduly burdensome application process. Although PRIME provides early scientific and regulatory support, companies often perceive FDA Breakthrough Therapy designation as offering more intensive and continuous engagement throughout development.

European companies entering U.S. development programs should budget significant time and resources for pre-IND meetings. These are not box-ticking exercises but genuine scientific dialogues that can reshape development strategies. Planning should begin well before the intended IND submission, typically once key preclinical studies are underway and the manufacturing process and initial clinical protocol have reached sufficient maturity to support meaningful discussion. Preparing for a pre-IND meeting often requires a cross-functional team, including regulatory affairs, CMC, nonclinical and clinical experts, with many first-time sponsors also engaging U.S. regulatory consultants or former FDA reviewers to help develop the briefing package and anticipate agency questions. While larger organizations may have dedicated regulatory staff with FDA experience, smaller European biotechnology companies frequently rely on external expertise to navigate the process effectively.

CMC Requirements And RNA-Specific Guidance

FDA expectations for mRNA therapeutics, reflected in agency guidance on oligonucleotide therapeutics, manufacturing comparability, and publicly communicated CMC review practices, have established detailed expectations for sequence characterization, impurity profiling, analytical control, and comparability that often exceed those encountered in traditional European regulatory interactions.

A recurring challenge for European companies is that manufacturing and analytical packages developed to satisfy EMA expectations may require significant supplementation for FDA submissions. Early alignment with FDA on CMC strategy, ideally via a Type B, pre-IND meeting can prevent costly rework later.

Clinical Trials Regulation: IND (Investigational New Drug) Vs. CTA (Clinical Trial Authorization)

The U.S. IND process and the European CTA process differ substantially in structure, timing, and the degree to which the regulator intervenes prior to study start. The FDA’s 30-day IND review window, while often achievable, comes with the expectation of detailed preclinical and CMC packages that meet FDA-specific standards. European CTAs, particularly post-EU CTR implementation, have their own complexities, but the regulatory philosophy differs. The FDA acts more as an active gatekeeper, while European national competent authorities have historically been more variable in their depth of engagement.

Companies pursuing parallel U.S. and European clinical programs need to plan for the divergence, particularly around comparative safety reporting obligations, data monitoring committee charters, and informed consent requirements. These are manageable, but not trivial, and they require regulatory teams or advisors with genuine dual-jurisdiction experience.

Post-Market Approval Regulations

The FDA’s increasing emphasis on real-world evidence (RWE) frameworks and its post-approval commitments for novel modalities, including enhanced pharmacovigilance plans for RNA products add a layer of long-term regulatory engagement that European companies should model into their U.S. commercialization plans. The EMA has moved in a similar direction, but execution expectations and enforcement postures differ.

U.S. Market Entry Models For European Biotechs

European RNA companies typically enter the U.S. market through one of several models, each with distinct risk-reward profiles:

• Full U.S. Incorporation: A U.S. subsidiary with local leadership, particularly a U.S.-based chief medical officer or chief business officer, signals seriousness to investors and partners and enables direct FDA engagement. This is increasingly the expected model for companies seeking Series A and Series B funding or beyond from U.S. venture capital firms.
• U.S. Hub With European Operations: Many European companies establish a Boston, San Francisco, or New York presence often via a small team of two to five staff to manage business development, corporate finance and/or CFO, investor relations, and key opinion leader engagement before building out a full U.S. organization. Equally common is a dual-company structure, in which the European or U.K. entity remains the parent (TopCo), retaining intellectual property ownership and corporate governance, while a U.S. subsidiary (OpCo) is established to lead clinical development, regulatory interactions, commercial operations, and investor engagement. This approach enables companies to maintain their European corporate identity while establishing the local presence often expected by U.S. regulators, investors, partners, and talent.
• Virtual U.S. Presence Via Partnerships: Some earlier-stage companies choose to partner with a U.S.-based CRO or regulatory consultancy to run their IND program and initial U.S. clinical activities without establishing a legal entity. This preserves capital but may limit strategic flexibility.
• NASDAQ Listing: A U.S. IPO or NASDAQ listing is a path taken by a growing number of European RNA biotechs, but it comes with substantial corporate governance and compliance obligations and requires a credible U.S. institutional investor base, which typically needs to be built over 18 to 24 months before any listing.

Timing Of U.S. Market Entry

The most common strategic error I observe is premature U.S. entry: companies that establish a U.S. presence, hire a U.S. CMO, and begin FDA engagement before their data package is sufficiently mature. The result is a dilution of management focus, early capital burn, and interactions with the FDA that cannot be fully leveraged because the science is not yet ready.

Conversely, late entry – waiting until after European approval or advanced Phase 2 before engaging the FDA – leaves competitive ground ceded to U.S. or better-positioned rival companies. It can be argued that the optimal window for most RNA therapeutic companies is around the transition to clinical studies with sufficient safety and early efficacy data to anchor meaningful FDA dialogue but still enough flexibility to incorporate U.S.-specific development requirements into the pivotal program design.

Conclusion

Successfully entering the U.S. market requires far more than opening an office or filing an IND. It demands early regulatory planning, thoughtful timing, and an expansion strategy aligned with a company’s stage of development. Companies that invest in these fundamentals position themselves for stronger interactions with regulators, investors, and partners alike.

In Part 2, I’ll examine the financial and operational side of U.S. expansion, including fundraising, partnerships, manufacturing, legal considerations, and the practical lessons European biotech leaders have learned while building successful U.S. operations.

About The Author

Ahmet Berkyurek, Ph.D., is cofounder and CEO of CamMed. He completed master’s and doctorate degrees at Osaka University, with a research fellowship from the Japanese government, and a bachelor’s degree from Istanbul Technical University (ITU). Berkyurek continued his scientific career at the University of Cambridge as a research fellow with a Marie-Curie Fellowship and worked in the biotech industry at the intersection of biochemistry, cell biology, RNA biology, oligonucleotide, and vaccine/RNA therapeutics. Berkyurek was a finalist for Researcher of the Year 2023 by Cambridge Independent Science and Technology Awards for his discoveries in RNA therapeutics to prevent SARS-CoV-2 infections and received the CEO of the Year 2025 Award for the U.K. from the Global Excellence Network for his contributions to mRNA therapeutics research.

Additional contributions were made to this article by the following:

Virginia Castilla Llorente, Ph.D., chief scientific officer
Kenny Simmen, Ph.D., board member
Natalie Pankova, Ph.D., board member